{"id":1494,"date":"2024-03-12T17:11:13","date_gmt":"2024-03-12T21:11:13","guid":{"rendered":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/?post_type=chapter&p=1494"},"modified":"2025-10-17T19:31:06","modified_gmt":"2025-10-17T23:31:06","slug":"osteoarthritis-rheumatoid-arthritis-and-gouty-arthritis","status":"web-only","type":"chapter","link":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/chapter\/osteoarthritis-rheumatoid-arthritis-and-gouty-arthritis\/","title":{"raw":"Osteoarthritis, Rheumatoid Arthritis, and Gouty Arthritis","rendered":"Osteoarthritis, Rheumatoid Arthritis, and Gouty Arthritis"},"content":{"raw":"

Arthritis:<\/strong><\/h3>\r\nAs the names suggest, all 3 diseases (osteoarthritis, rheumatoid arthritis and gouty arthritis) are depicted by inflammation within articulations (most often within synovial joints).\r\n

Osteoarthritis:<\/strong><\/h1>\r\nIn the case of the most common joint disease, osteoarthritis<\/strong>, the degenerative loss of articular (hyaline) cartilage is associated with aging and wear and tear.\u00a0 Unfortunately, osteoarthritis is a source of chronic disability for millions of people worldwide.\u00a0 Approximately 4 million (>13%) Canadians and more than 30 million Americans have osteoarthritis, with over 50% of older adults affected.\r\n\r\n[caption id=\"attachment_2529\" align=\"alignnone\" width=\"300\"]\"Osteoarthritis<\/a> Osteoarthritis of a synovial joint results from aging or prolonged joint wear and tear. These cause erosion and loss of the articular cartilage covering the surfaces of the bones, resulting in inflammation that causes joint stiffness, joint narrowing, and pain.[\/caption]\r\n

Risk Factors - Osteoarthritis<\/strong><\/h3>\r\nBesides age, other risk factors include previous joint tissue damage due to trauma or infection. Genetics (e.g., genes that affect collagen levels), family history, obesity, repetitive use during heavy labour, reduced levels of sex hormones, reduced circulation, and diabetes mellitus.\u00a0 Biological females are more susceptible to osteoarthritis especially in knee and hand joints.\r\n\r\nPrevention strategies involve daily physical activity and maintenance of healthy weight, following national food guides and adhering to nutritional guidelines, as well as controlling diabetes mellitus\u00a0 and other risk factors.\r\n

Signs and Symptoms - Osteoarthritis<\/strong><\/h3>\r\nThe signs and symptoms<\/strong> include: joint pain, swelling, stiffness, crepitus, and limited range of motion.\u00a0 Although historically, osteoarthritis was considered non-inflammatory, analysis of synovial fluid and the cartilage have revealed pro-inflammatory cytokines and other signs of inflammation.\r\n\r\nMost often osteoarthritis affects the knees, hips and hands, though the weight-bearing lumbrosacral vertebrae and feet joints can also be affected.\u00a0 Typically, osteoarthritis develops bilaterally.\r\n\r\nAs the cartilage deteriorates, it is replaced by bony spurs, which can lead to pain, and more limited range of motion.\u00a0 With pain and stiffness, a limp and\/or predispositions to falls can develop.\r\n\r\nIn the case of osteoarthritis of the hand enlarged finger joints (knuckles) can also lead to difficulties in putting on rings or taking them off.\u00a0 Enlarged distal interphalangeal joints are called Heberden nodes, whereas enlarged middle interphalangeal joints are termed Bouchard's nodes.\u00a0 Heberden nodes develop more frequently in biological females in comparison with biological males.\r\n\r\nNot only do bony spurs (osteophytes) develop, but loss of cartilage leads to joint space narrowing as well as subchondral bone degeneration with the development of cysts.\u00a0 Should the osteophytes break loose, they become \"joint mice\" which can further limit range of motion and cause additional pain, damage, and crepitus.\u00a0 The term osteophytosis refers to the development of bone spurs in joints.\r\n\r\n[caption id=\"attachment_2507\" align=\"alignnone\" width=\"300\"]\"Phenotypes<\/a> Phenotypes of Osteoarthritis (OA). Clinic evidence shows that the majority of OA patients have a diversity of OA phenotypes, including articular cartilage erosion, synovial hyperplasia, abnormal angiogenesis, synovial inflammation, subchondral bone disturbance, ligaments and tendons instability, and joint stiffness. Left-half side shows the structure of the normal synovial joint. Right-half side shows the possible alterations of synovial joint structure and symptoms in osteoarthritis.[\/caption]\r\n

Diagnosis - Osteoarthritis<\/strong><\/h3>\r\nTypically, diagnosis of osteoarthritis involves imaging<\/strong> (e.g., x-rays, CT scans, MRI, ultrasound, bone scans), often to rule out other causes of the signs and symptoms experienced (e.g., osteomyelitis, bone cancer, or tears in the meniscus, tendons, or ligaments).\u00a0 At times arthrocentesis is used, and the synovial fluid is checked for signs of inflammation and infection.\r\n\r\nDuring diagnosis, osteoarthritis may be staged<\/strong> as involving: a) the surface, b) partial-thickness, or c) full-thickness without and then with subchondral bone damage and\/or cysts.\u00a0 This illustrates the pathogenesis of the disease, which can involve:\r\n
    \r\n \t
  1. The thick smooth articular cartilage erodes<\/strong> releasing proteoglycan and collagen fragments into the synovial fluid<\/li>\r\n \t
  2. Fibrillations<\/strong> (deep, long fissures) develop in the articular cartilage<\/li>\r\n \t
  3. Osteophytosis <\/strong><\/li>\r\n \t
  4. Subchondral bone remodelling<\/strong>\u00a0with areas of sclerosis<\/strong> (that have irregular thickening and increased bone density) areas that become cysts<\/strong><\/li>\r\n \t
  5. Fibrosis of the articular capsule<\/strong> surrounding the joint occurs<\/li>\r\n \t
  6. Synovitis<\/strong> develops and joint space narrows<\/li>\r\n \t
  7. Irritation of joint capsule sensory nerve endings<\/strong> and pain due to increased pressure, pro-inflammatory cytokines,<\/li>\r\n<\/ol>\r\n

    Treatment - Osteoarthritis<\/strong><\/h3>\r\nTreatments involve both non-pharmacological and pharmacological interventions as well as surgical interventions.\r\n\r\nNon-pharmacological interventions include: physical therapy, prescribed (often low-impact) exercise, and weight loss if and individual has excess weight that is contributing to joint deterioration and\/or pain.\u00a0 The use of warm and cold compresses can be helpful as can the use of orthotics in footwear.\u00a0 At times, canes and braces are used to provide support.\r\n\r\nMedications that are prescribed can include NSAIDs, acetaminophen, and glucocorticoid injections.\r\n\r\nSurgeries are performed using arthroscopy arthroplasty<\/strong> (joint replacements), and joint fusion<\/strong>.\u00a0 Arthroscopy can be used to remove loose articular cartilage, meniscus tears, and other loose bodies.\u00a0 Arthroplasty involves removal of joint surface and inserting metal and plastic prothesis that can be anchored in place with bone cement or bone ingrowth into porous coating of prothesis.\u00a0 Joint fusion involves uniting bones on either side of the joint, which can be helpful removing pain, but limits motion.\u00a0 Surgery carries the (usually small) risk of infection and formation of thrombi (blood clots) and emboli.\r\n\r\nComplimentary therapies such as physical therapy, massage therapy, and acupuncture are sometimes utilized.\r\n\r\n \r\n

    Rheumatoid Arthritis:<\/strong><\/h1>\r\nRheumatoid arthritis (RA) affects approximately 1% of the population and is thought to be caused by an autoimmune disease, that results in progressive damage to joints.\u00a0 In addition to causing chronic inflammation and deterioration of the affected joints, vasculitis, pericarditis, and at times damage to the lungs, heart, eyes, and skin can occur.\r\n\r\n[caption id=\"attachment_2577\" align=\"alignnone\" width=\"300\"]\"Rheumatoid<\/a> Rheumatoid arthritis is an autoimmune disease that causes the immune system to attack healthy cells of the body, primarily affecting joints resulting in painful inflammation.[\/caption]\r\n

    Risk Factors - Rheumatoid Arthritis<\/strong><\/h3>\r\nGenetics are thought to account for 50% of the risk for developing RA, specifically the inheritance of certain alleles (or variations) of the Major Histocompatibility Complex (MHC) genes.\u00a0 Another major risk factor for developing RA is biological sex.\u00a0 It is unclear why RA affects approximately 3 times as many biological females as males, though differing levels of sex hormones are thought to be a contributing factor.\u00a0 This is theory is potentially supported by the fact that pregnancy and even for 1-5 years post-partum can result in a remission (relapse of symptoms).\u00a0 \u00a0The role of sex hormones on the immune response has been under investigation for some time.\u00a0 Other risk factors include previous infections (e.g., Epstein-Barr Virus, EBV), trauma, as well as smoking.\u00a0 There are dietary risk factors as well including alcohol consumption.\u00a0 Healthy lifestyle, on the other hand, has been associated with the lower risks of developing RA.\r\n\r\n[caption id=\"attachment_2530\" align=\"alignnone\" width=\"300\"]\"Comparison<\/a> Comparison of Normal Joint and Rheumatoid Arthritis[\/caption]\r\n\r\n \r\n

    Pathogenesis - Rheumatoid Arthritis<\/strong><\/h3>\r\nRA begins when the body's immune system starts to recognize and launch an attack against self-antigens within its own synovial joints.\u00a0 Both activated T and B lymphocytes are involved and B cells produce autoantibodies<\/strong> (termed Rheumatoid Factors<\/strong>, RFs) that target the joint for destruction.\u00a0 40% of patients also develop antinuclear antibodies (ANA).\u00a0 Macrophage production of pro-inflammatory cytokines increases the inflammation and chronic destruction within the joint.\u00a0 Synovitis<\/strong> occurs with cell proliferation creating an inflamed thickened synovial membrane.\u00a0 The formation of pannus<\/strong> (fibrovascular tissue or granulation tissue) containing new connective tissue and tiny blood vessels occurs over portions of the joint surface.\u00a0 Articular cartilage erodes.\u00a0 Progressive damage of cartilage, bone, tendons and ligaments occurs.\u00a0 Fibrous (scar) tissue may form and calcify within the joint space.\u00a0 If this calcified fibrous tissue crossed the joint space and bridges the two bones, joint fixation, loss of range of motion as well as joint deformity may develop if not treated.\u00a0 The term ankylosis<\/strong> is used in this type of instance to describe the fusion of bones resulting in joint immobility.\u00a0 Vasculitis can develop anywhere in the body, but may be seen in the skin in the form of purpura (small red-ish spots due to small blood vessel leaks).\u00a0 Vascular damage makes an individual more prone to atherosclerosis, myocardial infarction and stroke (i.e., cerebrovascular accident, CVA).\u00a0 Lung inflammation and fibrosis may also occur.\r\n\r\n[caption id=\"attachment_4529\" align=\"alignnone\" width=\"300\"]\"Comparison<\/a> Comparison of Normal and Rheumatoid Arthritis joints. Rheumatoid Arthritis is characterized by bone, synovial membrane, and cartilage erosion and the presence of overactive leukocytes.[\/caption]\r\n

    Signs and Symptoms - Rheumatoid Arthritis<\/strong><\/h3>\r\nSigns and symptoms have an insidious onset and include:\u00a0 symmetrical, swollen, painful, stiff joints most often in the hands, knees, hips and feet as well as fatigue, malaise and sometimes fever.\u00a0 There can be periods of relapse and exacerbation.\u00a0 As joints are damaged, deformities in the hands begin to appear (e.g., boutonni\u00e8re and swan neck deformities).\u00a0 RA can lead to osteopenia or osteoporosis which put one at risk for vertebral compression fractures and hip fractures.\u00a0 Other signs and symptoms include the development of subcutaneous nodules that might be seen in the skin on hands, elbows, etc.\u00a0 Unfortunately, as this disease progresses, individuals can begin to have difficulty performing daily activities and approximately 40% of individuals become disabled.\u00a0 Early treatment is recommended to offset and slow down the progression of the disease.\r\n\r\n[caption id=\"attachment_2531\" align=\"alignnone\" width=\"300\"]\"Swan<\/a> Swan neck deformity in a 65 year old patient with Rheumatoid Arthritis[\/caption]\r\n

    Diagnosis - Rheumatoid Arthritis<\/strong><\/h3>\r\nRheumatoid arthritis is diagnosed based on patient history, physical examination of involved joints, imaging (e.g., x-rays, ultrasound), and blood tests.\u00a0 Imaging can reveal destruction of cartilage, bone, tendons and ligaments.\u00a0 Blood tests often reveal inflammation through elevated levels of Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP).\u00a0 Blood tests and analysis of synovial fluid reveal high levels of RF.\r\n

    Treatment - Rheumatoid Arthritis<\/strong><\/h3>\r\nTreatments include: hot and cold compresses, therapeutic exercises, the use of orthotics, glucocorticoids, NSAIDS, Disease-Modifying antirheumatic drugs (DMARDs) and various surgeries as required.\u00a0 Surgery options such as synovectomy, tendon realignment, and arthroplasty (joint replacement) are performed as necessary.\u00a0 Often individuals are treated with immunosuppressive drugs (e.g., DMARDs) which puts them at greater risk for infections.\r\n\r\nNon-pharmacological treatments include: physical therapy, prescribed (often low-impact) exercise, and weight loss if and individual has excess weight that is contributing to joint deterioration and\/or pain.\u00a0 At times, canes, braces and other assistive devices are used to provide support.\r\n

    Gouty Arthritis:<\/h1>\r\nGouty arthritis is caused by the build up of uric acid crystals within joints causing irritation and inflammation.\r\n

    Pathogenesis - Gouty Arthritis<\/strong><\/h3>\r\nPurines such as adenine and guanine are nitrogenous bases that have several roles in human cells.\u00a0 For example, adenine and guanine form two of the four nucleobases used to make deoxyribose nucleic acid (DNA).\u00a0 Adenine and guanine are also used to make high energy fuel molecules, adenosine triphosphate (ATP) and guanine triphosphate (GTP).\u00a0 Purine turnover occurs naturally in all nucleated cells.\u00a0 The breakdown of purines (purine metabolism) produces the waste product, uric acid, which enters the bloodstream and then is removed from the blood stream by the renal nephrons (of the kidneys).\u00a0 If uric acid isn't eliminated quickly enough (in the form of urine), either due to inefficient elimination (in 90% of cases) or due to overconsumption of purines (<10% of cases), then uric acid can build up in the blood stream which is termed hyperuricemia.\r\n\r\nConsuming large amounts of purine-rich foods (e.g., anchovies, sardines, organ meats) or purine-rich beverages (beer, hard liquor) puts a person at risk for hyperuricemia.\r\n\r\nHyperuricemia pre-disposes to the accumulation of uric acid crystals in synovial fluid, as well as in skin, cartilage, tendon, ligament, and kidney.\u00a0 Within joints, accumulations or urate crystals form microtophi and then larger tophi.\u00a0 Often this occurs over a long stretch of time 10-20 years, before tophi and signs and symptoms of gout develop (most commonly at 30-60 years of age).\r\n\r\nA tophus is a subcutaneous hard nodule filled with uric acid crystals that is surrounded by a zone of inflammation and is visible in the affected joints.\u00a0 The uric acid crystals are irritating to cells in the region including macrophages which trigger an immune response.\u00a0 Activated neutrophils migrate to the area releasing inflammatory compounds that cause pain and deterioration of the joint if not treated.\r\n\r\nStrangely, there is a seasonality to gout flares with spring and summer being peaks times of year which correlates with cortisol levels dropping and levels of neutrophils increasing.\u00a0 \u00a0This may not be a coincidence due to the inflammatory role of gout flares.\u00a0 Interestingly not everyone with hyperuricemia develops gout, there appears to be genetic susceptibilities involved as well as differences in gut microflora (and the metabolism of urate by gut flora).\r\n

    Risk Factors- Gouty Arthritis<\/strong><\/h3>\r\nRisk factors for gout include:\u00a0 genetics (and therefore family history), alcoholism, diet, obesity, biological sex, and age.\u00a0 It has been found that estrogen provides biological females with a uricosuric effect (i.e., estrogen promotes the secretion and elimination of uric acid by nephrons).\u00a0 Therefore, biological males are more at risk for gout than pre-menopausal females, as are individuals that have a diet high in purine-rich foods (e.g., meat and seafood) or drink (e.g., beer and hard liquor).\u00a0 Chemotherapy treatment is also a risk factor as there is an increased breakdown of cellular DNA.\u00a0 Other risk factors include diabetes, hypertension, kidney disease, use of diuretics, and age (post-menopausal for females).\r\n

    Signs and Symptoms- Gouty Arthritis<\/strong><\/h3>\r\nWhile the development of tophi within joints can take a long time (10-20 years), the pain and inflammation that suddenly occurs is acute, displaying all of the signs of inflammation warmth, redness, swelling, and pain that is usually extreme.\u00a0 Frequently the big toe joints are affected, though other joints can also be affected as well (e.g., ankle, wrist, finger, and knee are among the more common ones).\u00a0 Inflammation of the proximal big toe joint was termed podagra by the Ancient Greeks which translates as \"foot-grabber\" which now may a good way to remember the unpleasant pain associated with gout.\u00a0 The swelling can limit range of motion and be accompanied by fever.\u00a0 As hyperuricemia also puts one at risk for kidney stones, signs and symptoms of renal calculi (kidney stones) may occur at the same time (or before or after).\r\n

    Diagnosis- Gouty Arthritis<\/strong><\/h3>\r\nDiagnosis typically involves physical examination and aspiration of synovial fluid<\/strong> to analyze for monosodium urate crystals and rule out other causes of inflammation and pain (e.g., infection).\u00a0 Blood<\/strong> and urine<\/strong> tests can be performed as well to determine the levels of urea and uric acid in the blood and urine.\u00a0 X-rays<\/strong> can be used to assess any erosions of bone or cartilage in addition to any changes in joint space.\u00a0 Ultrasound<\/strong> can be used to detect signs of crystal formations and bone erosion.\r\n

    Treatment- Gouty Arthritis<\/strong><\/h3>\r\nTreatment often involves treating the joint that is affected as well as taking steps to avoid future episodes.\u00a0 Pharmacological treatment may include: NSAIDs, glucocorticoids, and other medications.\r\n\r\nTypically, surgical removal of tophi only occurs, when infection, joint deformity is present as other interventions (medications) lead to better outcomes and faster healing.\r\n\r\nLifestyle changes are often recommended which include reducing consumption of high-purine foods, alcohol, high-fat foods, sugary foods, sugary drinks, and increasing levels of water intake to approximately 8 glasses of water per day.\u00a0 Establishing a healthy weight and diet coupled with daily physical activity is recommended.\r\n

    Arthritis Summary<\/span><\/h1>\r\n
    \r\n

    Key Take Aways - Specific Learning Objectives Study Guide<\/strong><\/p>\r\n\r\n<\/header>\r\n

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    Osteoarthritis:<\/strong><\/h2>\r\nan inflammatory joint disease due to \"wear and tear\", most often affecting hips and knees<\/span>\r\n\r\n \r\n
    Risk factors:<\/strong><\/div>\r\n